A Practical Synthesis of an Aminopyridine as a Component of a BTK Inhibitor

作者：Alabanza Lady Mae; Dong Yan; Wang Ping; Wright James A; Zhang Yingchao; Briggs Andrew J^*

来源：Organic Process Research & Development, 2013, 17(5): 876-880.

DOI：10.1021/op400046y

Development of a new route to the BTK intermediate, 5-(1-(azetidin-1-yl)-2-methylpropan-2-yloxy)pyridin-2-amine (7), has resulted in significant improvements in terms of yield, purity, and operability over the previously known synthesis. The new route was demonstrated on a multihundred-gram scale, and the overall yield of 7 from 2-chloro-5-hydroxypyridine (1) was improved to 72%. Lithium aluminum hydride, a Swern oxidation, cesium carbonate, azetidine free base, and four chromatographic purifications used in the earlier synthesis were eliminated.

• 出版日期2013-5